PSMA-Specific CAR-Engineered T Cells Eradicate Disseminated Prostate Cancer in Preclinical Models.

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Version: author
Serval ID
serval:BIB_0E434AE25E35
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PSMA-Specific CAR-Engineered T Cells Eradicate Disseminated Prostate Cancer in Preclinical Models.
Journal
Plos One
Author(s)
Zuccolotto G., Fracasso G., Merlo A., Montagner I.M., Rondina M., Bobisse S., Figini M., Cingarlini S., Colombatti M., Zanovello P., Rosato A.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
9
Number
10
Pages
e109427
Language
english
Notes
Publication types: Journal Article Publication Status: epublish
Abstract
Immunology-based interventions have been proposed as a promising curative chance to effectively attack postoperative minimal residual disease and distant metastatic localizations of prostate tumors. We developed a chimeric antigen receptor (CAR) construct targeting the human prostate-specific membrane antigen (hPSMA), based on a novel and high affinity specific mAb. As a transfer method, we employed last-generation lentiviral vectors (LV) carrying a synthetic bidirectional promoter capable of robust and coordinated expression of the CAR molecule, and a bioluminescent reporter gene to allow the tracking of transgenic T cells after in vivo adoptive transfer. Overall, we demonstrated that CAR-expressing LV efficiently transduced short-term activated PBMC, which in turn were readily stimulated to produce cytokines and to exert a relevant cytotoxic activity by engagement with PSMA+ prostate tumor cells. Upon in vivo transfer in tumor-bearing mice, CAR-transduced T cells were capable to completely eradicate a disseminated neoplasia in the majority of treated animals, thus supporting the translation of such approach in the clinical setting.
Pubmed
Web of science
Open Access
Yes
Create date
06/11/2014 19:08
Last modification date
20/08/2019 12:35
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